The NGERC seeks to advance research on the antecedents of neurodevelopmental schizophrenia, i.e., on the origins and early manifestations of neurodevelopmental disturbance in this disorder. We will use data from life course cohorts that have been followed from early life and are now either in the age of risk for schizophrenia. Drawing on the resources and infrastructure of the MHCRC, we propose to extend the uses of the data for each of three types of life course cohorts: population- based birth cohorts, genetic high-risk cohorts, and epigenetic high-risk cohorts. Population-based birth cohorts are unselected for any specific etiology, whereas a genetic high-risk cohort is selected so as to be enriched for genetic etiology, and an epigenetic high-risk cohort is selected so as to be enriched for an environmental factor which can impact on genetically programmed neurodevelopment (e.g., prenatal brain insult). The specific aims are to investigate antecedents of neurodevelopmental schizophrenia in: 1. a collaborative study that combines data across four birth cohorts. This study includes the large Oakland Child Health and Development Study birth cohort together with three cohorts derived from the multi-site National Collaborative Perinatal Project. Each cohort was based on births during 1959-1966, was followed from the prenatal period into childhood or later, and is currently being followed up for schizophrenia by Co- investigators in this proposal. Taken alone each cohort has limited statistical power, especially for rare exposures. By contrast, the combined sample of approximately 30,000 live births provide adequate power for a comprehensive investigation. Using the infrastructure of the MHCRC, we will be able to create a combined database, conduct collaborative research, and make this database a resource for other schizophrenia researchers. 2. a cohort enriched for genetic etiology. In the New York High-Risk Project, of L. Erlenhmeyer-Kimling of the NGERC, 324 offspring of schizophrenic, affectively ill, and normal parents have been followed into mid-adulthood. The present study undertakes to extend the data analysis to focus on early manifestations of neurodevelopmental disturbance in schizophrenia. 3. a cohort enriched for epigenetic etiology. in the Rubella Birth Defects Evaluation Project, 70 individuals exposed to rubella during gestation have been followed into adulthood and have been shown to have a greatly increased risk of schizophrenia. The present study will extend the collection and uses of family history and brain imaging data. While the other Cores of the MCHRC are essential to all three aims, this Core in turn is designed to contribute to each of the other Cores, not only by providing unique data, but also by fostering interdisciplinary research that is jointly conceived and conducted.